期刊
NEUROTOXICOLOGY
卷 33, 期 1, 页码 85-90出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.neuro.2011.12.005
关键词
Amyloid-beta; Coenzyme Q10; Oxidative stress; Neuroprotection; Phosphatidylinositol 3-kinase
资金
- National Research Foundation of Korea (NRF) [2010-0009588]
- Korea Healthcare Technology RD Project
- Ministry for Health, Welfare & Family Affairs, Republic of Korea [A101712]
- National Research Foundation of Korea [2010-0009588] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Oxidative stress plays critical roles in the pathogenic mechanisms of several neurodegenerative disorders including Alzheimer's disease (AD), thus much research effort has focused on antioxidants as potential treatment agents for AD. Coenzyme Q10 (CoQ10) is known to have powerful antioxidant effects. We investigated the neuroprotective effects of CoQ10 against Amyloid beta(25-35) (A beta(25-35))-induced neurotoxicity in rat cortical neurons. To evaluate the neuroprotective effects of CoQ10 on A beta(25-35)-injured neurons, primary cultured cortical neurons were treated with several concentrations of CoQ10 and/or A beta(25-35) for 48 h. CoQ10 protected neuronal cells against A beta(25-35)-induced neurotoxicity in a concentration-dependent manner. These neuroprotective effects of CoQ10 were blocked by LY294002 (10 mu M), a phosphatidylinositol 3-kinase (P13K) inhibitor. A beta(25-35) concentration-dependent increased free radical levels in rat cortical neurons, while combined treatment with CoQ10 reduced these free radical levels in a dose-dependent manner. Meanwhile. CoQ10 treatment of A beta(25-35)-injured primary cultured cortical neurons increased the expression levels of p85aP13K, phosphorylated Akt, phosphorylated glycogen synthase kinase-3 beta, and heat shock transcription factor, which are proteins related to neuronal cell survival, and decreased the levels of cytosolic cytochrome c and cleaved caspase-3, which are associated with neuronal cell death. Together, these results suggest that the neuroprotective effects of CoQ10 on A beta(25-35) neurotoxicity are mediated by inhibition of oxidative stress together with activation of the P13-K/Akt pathway. (C) 2011 Elsevier Inc. All rights reserved.
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